Summary of Work: Cigarette smoking during pregnancy may have adverse effects on the developing fetal respiratory tract, with possible functional deficits in the newborn. Two major components of cigarette smoke, cadmium (CdCl2) and nicotine were administered to pregnant rats and potential developmental toxicity for the neonatal respiratory tract was evaluated. In utero exposure to relatively high levels of CdCl2 caused an increased number of pup deaths on postnatal day 1(PND1); nicotine had no effect. Lungs of pups from CdCl2-treated dams had high levels of glycogen relative to controls suggesting that in utero exposure to CdCl2 may interfere with glycogen utilization resulting in an inhibition of surfactant production in the fetal lung and neonatal death. Measurement (ELISA) of surfactant protein A (SP-A), as an estimate of surfactant levels, showed no significant difference between controls and CdCl2 or nicotine-treated groups. Additional experiments are being conducted to measure total phospholipid as a more accurate estimate of surfactant levels in fetal lungs. Lung changes in glycogen, and expression of surfactant apoprotein mRNA in fetal and neonatal lungs also will be measured. To determine if irreversible effects are caused by in utero exposure, neonates at various ages will be evaluated for abnormalities in histological and biochemical indices of pulmonary development, and abnormal changes in pulmonary function in response to chemical challenge. In addition, the potential effects of in utero exposure to mercury on pulmonary development are being evaluated. Mercury had no effect on neonatal viability; neonatal lung SP-A levels are being measured.